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- Title
Three- vs Four-Drug Antiretroviral Regimens for the Initial Treatment of HIV-1 Infection.
- Authors
Gulick, Roy M.; Ribaudo, Heather J.; Shikuma, Cecilia M.; Lalama, Christina; Schackman, Bruce R.; Meyer III, William A.; Acosta, Edward P.; Schouten, Jeffrey; Squires, Kathleen E.; Pilcher, Christopher D.; Murphy, Robert L.; Koletar, Susan L.; Carlson, Margrit; Reichman, Richard C.; Bastow, Barbara; Klingman, Karin L.; Kuritzkes, Daniel R.
- Abstract
Context Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen. Objective To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection. Design The AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double- blind, placebo-controlled study with enrollment and follow-up conducted from March 22,2001, to March 1,2005, and enrolling treatment-naive, HIV-1-infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG. Interventions Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen). Main Outcome Measures Time to virologic failure (defined as time to first of 2 successive HIV-1 RNA levels ≥200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes. Results Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log10 (72 444) copies/mL and CD4 cell count of 240 cells/mm3 were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69-1.33; P= .73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95% confidence interval, 1.18-2.34; P=.003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively (P=.59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P=.39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different. Conclusions In treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit.
- Subjects
ANTIRETROVIRAL agents; CLINICAL drug trials; HIV infections; THERAPEUTICS; AIDS treatment; VIRUS research; RANDOMIZED controlled trials; MEDICAL research
- Publication
JAMA: Journal of the American Medical Association, 2006, Vol 296, Issue 7, p769
- ISSN
0098-7484
- Publication type
Article
- DOI
10.1001/jama.296.7.769